Background: Immunoglobulin G4 (IgG4) is an emerging biomarker and therapeutic target in autoimmune diseases. Studies have shown that the levels of IgG4 are elevated in rheumatoid arthritis (RA) patients, particularly in those with extra-articular manifestations such as scleritis and vasculitis. The role of IgG4 in RA with regard to disease severity and disease activity remains vague. The therapeutic implications of targeting IgG4 in RA appears promising based on preliminary data.

Objectives: This study aimed to compare IgG4 with other inflammatory cytokines that have been implicated in the pathogenesis of RA namely interleukin 1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor- α (TNFα). We studied the relationship of IgG4 and the aforementioned cytokines with disease activity, radiographic joint damage and functional disability.

Methods: We consecutively recruited 194 patients with RA from our rheumatology clinic. We excluded patients with (a.) overlap syndrome with other connective tissue diseases such as Systemic Lupus Erythematosus, Systemic Sclerosis, and Polymyositis; (b.) pregnant RA patients as radiographic assessment was contraindicated; (c.) patients with concomitant malignancy; and (d.) patients with acute infections. All subjects were assessed for their disease activity based on DAS28, radiographic joint damage based on Modified Sharp Score (MSS), functional capacity based on Health Assessment Questionnaire –Disability Index (HAQ-DI). Serum IgG4, IL-1, IL-6 and TNFα of the recruited subjects were measured via ELISA test.

Results: The mean serum IgG4 level was 60.23 ± 30.08 mg/dL. We found that serum IgG4 had significant positive correlations with disease activity (r=0.278; p=0.002), ESR (r=0.143; p=0.048), radiographic joint damage (r=0.237; p=0.001) and functional disability (r=0.769; p=0.001). However, only IL-6 (p=0.001) had a significant correlation with IgG4 compared to the other cytokines. On multivariate analysis, only HAQ-DI (p=0.001) and MSS (p=0.032) remained significantly associated with serum IgG4. IL-1 and IL-6 showed significant positive correlations with DAS28 scores.

Conclusion: Serum IgG4 appears to be a promising biomarker of disease activity, joint damage and functional disability in RA. The role of IgG4 in RA is probably comparable; if not more important than pro-inflammatory cytokines. Further research is needed to elucidate the precise mechanisms by which IgG4 is involved in the pathogenesis of RA.

REFERENCES: [1] Chen L-F, Mo Y-Q, Ma J-D, Luo L, Zheng D-h, Dai L. Elevated Serum IgG4 Defines Specific Clinical Phenotype of Rheumatoid Arthritis. Mediators of Inflammation. 2014;2014:635293.

[2] Kim S-H, Jeong H-J, Kim J-M, Jun J-B, Son C-N. Clinical Significance of Elevated Serum Immunoglobulin G4 Levels in Patients With Rheumatoid Arthritis. Journal of Rheumatic Diseases. 2020;27(2):96.

[3] Bos WH, Bartelds GM, Vis M, Van Der Horst AR, Wolbink GJ, Van De Stadt RJ, et al. Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases. 2009;68(4):558-63.

Acknowledgements: Ministry of Education, Malaysia (KPT) for FRGS grant (FRGS/1/2021/SKK08/UKM/02/1).

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.